Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma

Article type: Research Article

Authors: Dobrescu, Ruxandra^{a; b; *} | Schipor, Sorina^b | Manda, Dana^b | Caragheorgheopol, Andra^b | Badiu, Corin^{a; b}

Affiliations: [a] “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania | [b] “CI Parhon” National Institute of Endocrinology, Bucharest, Romania

Correspondence: [*] Corresponding author: Ruxandra Dobrescu, “CI Parhon” National Institute of Endocrinology – Scientific Laboratory, 34-38 Aviatorilor Blvd, Bucharest, Romania. Tel.: +40 724581325; E-mails: [email protected] and [email protected].

Abstract: BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of tumor initiation and progression. The MMP-9 promoter -1562C/T functional polymorphism increases gene expression and was identified as a susceptibility factor for various cancers. OBJECTIVE: To evaluate the influence of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the clinical and pathological phenotype. METHODS: We evaluated 236 patients with nodular thyroid disease pre-thyroidectomy (119 benign disease, 117 PTC). Genomic DNA was isolated from whole blood and the MMP-9 -1562C/T genotype was evaluated by PCR-RFLP analysis. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. The T allele was significantly more frequent in cancer compared to benign disease (17.5% vs 10.1%), p= 0.019. Patients with the CT or CT+TT genotype had an increased risk of developing PTC, specifically micropapillary thyroid carcinoma (MPTC) (CT genotype: OR = 6.467, p= 0.00006; CT+TT: OR = 6.859, p= 0.00002), but not more advanced stages (CT: p= 0.094; CT+TT: p= 0.157). The -1562C/T genotype did not significantly correlate with tumor histological subtype, invasion or TNM stage. CONCLUSION: The MMP-9 -1562C/T functional polymorphism may indicate susceptibility to develop thyroid cancer, specifically intrathyroidal clinically non-relevant MPTC. This suggests that although this genotype might be a predisposing factor, other genetic/epigenetic events are needed for cancer progression.

Keywords: Metalloproteinase-9, MMP-9, polymorphism, cancer susceptibility, thyroid cancer

DOI: 10.3233/CBM-203119

Journal: Cancer Biomarkers, vol. 34, no. 4, pp. 555-562, 2022